In the body, bones have important functions. Particularly, bones provide a frame to keep the body supported and act as a reserve of minerals important to the body, most notably calcium and so play an important role in regulating the calcium balance of bloodstream. To do so, the bone maintains homeostasis through bone resorption and remodeling. Accordingly, the bone is in a dynamic state, exhibiting a metabolic balance between bone resorption and bone formation.
Osteoporosis is a bone disease that leads to an increased risk of fracture because the bone density is reduced and bone microarchitecture is disrupted with the enlargement of the medullary cavity. With the elongation of human longevity, there has been a significant increase in osteoporosis.
Osteoporosis is caused by various factors including heredity, menopause, hyperthyroidism, hyperparathyroidism, chronic renal failure, the administration of adrenocortical hormones, etc. The highest prevalence of osteoporosis is found in women who have had the experience of menopause. The estrogen deficiency following menopause is correlated with a significant increase in osteoclastic bone resorption relative to osteoblastic bone formation and with a reduction in the intestinal absorption of calcium, giving rise to trabecular bone loss, that is, a decrease in bone mineral density (BMD).
Acting as selective inhibitors of osteoclast-mediated bone resorption, bisphosphonate-based drugs have been used for the antiresorptive treatment for osteoporosis. Bisphosphonate-based drugs cause calcium to be introduced into bone, resulting in a reduction in calcium blood level. Thus, the use of bisphosphonate-based drugs must be followed by calcium supplement. In recent years, unit formulations comprising bisphosphonate and vitamin D necessary for calcium absorption have been developed, and are commercially available (for example, Fosamax Plus).
Ibandronic acid, known as a potent bisphosphonate drug with high calcium binding affinity, is developed in the form of either single-ingredient tablets or injections. Despite great demand therefor, a formulation in which ibandronic acid and vitamin D are combined in a single dosage form is difficult to prepare due to the differences in their physical properties.